The Agricultural Health Study (AHS) is a long-term prospective study of potential health effects associated with exposure to pesticides and other agricultural exposures. The study is a collaboration of the National Cancer Institute, the National Institute of Environmental Health Sciences, and the US Environmental Protection Agency, with additional collaboration by the National Institute for Occupational Safety and Health. We are examining cancer incidence and other health endpoints in a prospective study of licensed pesticide applicators, spouses and children from North Carolina (NC) and Iowa (IA). Over a 3-year period (1993-7), we enrolled more than 57,000 licensed applicators, representing 82% of eligible private pesticide applicators (largely farmers) in IA and NC and 43% of commercial applicators from Iowa. About 40% of the private applicators also completed a more detailed take-home questionnaire covering farming practices and health. Nearly 32,000 spouses of farmer applicators enrolled and 2/3 of these also provided data on reproductive health, including information on all children under age 21. Since enrollment, 70% of participants completed the five-year followup phone interview (1999-2003) and the study is on track to achieve a similar response rate in our current followup phone interview.[unreadable] [unreadable] Annually, cancer incidence among the applicators, spouses, and children is determined through linkage with the population-based cancer registries in IA and NC. Follow-up computer-assisted telephone interviews are used to update exposure information, identify cases of non-malignant disease, and to collect information on changes in health status since enrollment in the study. We are currently completing the second round of followup with cohort members. Buccal-cell samples have been collected from participants in order to extract DNA for future analyses of gene and environment interactions. In addition, a dietary assessment (food frequency questionnaire) was self-completed and returned by mail. In-depth assessment of agricultural exposures has been done for a small sample of farmers and their families in order to validate the questionnaires and facilitate exposure classification. Both environmental and biological samples were collected. [unreadable] Non-cancer outcomes of particular interest in this follow-up period include neurological diseases and symptoms (Parkinson's Disease, hearing loss, depression, and neurobehavioral function), respiratory and allergic outcomes (asthma, rhinitis, chronic bronchitis, respiratory mortality), heart attacks (incidence and mortality), diabetes (both gestational and in adults), autoimmune diseases (rheumatoid arthritis), age-related macular degeneration, and reproductive outcomes (fertility, birthweight, pre-eclampsia, spontaneous abortion) in addition to cancer. [unreadable] We are currently involved in a number of substudies to collect more detailed information on potential health consequences of pesticides. The Growth and Puberty (GAP) Study is an intramurally-funded pilot study to assess the feasibility of measuring early puberty markers (hormone levels in urine and saliva, height velocity, Tanner staging) among farm children in the AHS. This study has enrolled approximately 60 children and the last of the three home visits will be completed by December 2008. The Genes and Age Related Macular Degeneration (GENARM) Study is obtaining medical records, opthamalogical photographs, and saliva as a source of DNA for individuals who reported incident macular degeneration at one of the followup interviews. Field work is completed and data analysis is ongoing. In a collaboration with Frederic Gerr at the University of IA, we conducted a study of neurobehavioral function using a number of standardized tests. Over 700 farmers participated and we are currently analyzing specimens for paraoxonase activity and genes related to organophosphate metabolism. Two more (parkinsons disease and lung health) are described in separate annual reports.[unreadable] [unreadable] Recent results from the Agricultural Health Study include: 1) Significant association of allergic asthma in adults with pesticide use, particularly organophosphate insecticides which have been shown in animal models to increase allergic airway responsiveness, 2) incident diabetes associated with use of specific pesticides (organochlorines: aldrin, chlordane, and heptachlor; organophosphates: dichlorvos and trichlorfon, and herbicides: alachlor and cyanazine), in a dose-dependent manner, and 3) hearing loss associated with long term pesticide use. [unreadable] We continue to analyze cross-sectional data on farm exposures and specific respiratory diseases, including adult onset asthma and respiratory mortality. Other work focuses on preeclampsia and use of pesticides during pregnancy as well as other adverse pregnancy and birth outcomes, uterine fibroids, macular degeneration, and risk for cardiovascular mortality and incident type II (adult onset) diabetes. Follow-up telephone interviews are being conducted and will be completed in FY2010.